Phase IIa/b Trial of PvCS/Montanide ISA-51 Malaria Vaccine in Adults in Chocó, Colombia

NCT07373301 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2201-3
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical study will evaluate an investigational malaria vaccine called PvCS/Montanide ISA-51 to determine whether it is safe and whether it can protect adults from infection with Plasmodium vivax, one of the main parasites that causes malaria. P. vivax malaria is common in tropical regions, including Colombia, and can lead to recurrent fever, anemia, and prolonged illness. Currently, no licensed vaccine effectively prevents P. vivax infection. The investigational vaccine (PvCS) contains synthetic peptides derived from the circumsporozoite (CS) protein located on the surface of P. vivax sporozoites. The vaccine is formulated with the adjuvant Montanide ISA-51 to enhance the immune response. This study aims to assess the safety of the PvCS/Montanide ISA-51 formulation and to determine whether it can prevent malaria after controlled exposure to the parasite. This is a Phase IIa/b, randomized, double-blind, placebo-controlled clinical trial conducted by the Malaria Vaccine and Drug Development Center (MVDC/CIV) in collaboration with ASOCLINIC IPS and the Pacific Health Institute (INSALPA) in Quibdó, Chocó, Colombia. A total of 72 healthy adults aged 18-50 years from malaria-endemic areas will participate. Participants will be randomly assigned in a 2:1 ratio to receive either the PvCS/Montanide ISA-51 vaccine or a placebo. The study product will be administered by intramuscular injection at months 0, 2, and 4. After each vaccination, participants will be monitored for side effects and provide blood samples to measure immune responses, including antibody levels and T-cell activity. Approximately one month after the third vaccination, participants will undergo a controlled human malaria infection (CHMI), during which they will be exposed to P. vivax through the bite of infected mosquitoes under strict medical supervision. Following exposure, participants will be monitored daily using blood tests to detect malaria at the earliest stage. If malaria parasites are detected-or if 21 days pass without infection-participants will receive prompt, effective antimalarial treatment based on Colombian national guidelines. All participants will continue to be followed for up to 12 months after the challenge to ensure safety and assess long-term outcomes. Primary goals of the study include: Determining whether the PvCS/Montanide ISA-51 vaccine prevents P. vivax infection after CHMI. Measuring the time between exposure and first detection of parasites (pre-patent period). Evaluating the safety and tolerability of the vaccine. Secondary goals include: Measuring immune responses generated by the vaccine. Exploring relationships between immune responses and protection from infection. The total duration of the study is expected to be approximately 30 months, including recruitment, immunizations, challenge procedures, and follow-up. Results will help determine whether this vaccine can safely protect adults against P. vivax malaria and guide planning for future larger-scale vaccine trials in endemic populations.

Conditions

Plasmodium Vivax Malaria; Plasmodium Vivax Infection; Malaria Prevention

Keywords

PvCS Vaccine; Plasmodium vivax; Malaria Vaccine; Montanide ISA-51; Controlled Human Malaria Infection; Malaria Prevention; Phase II Clinical Trial; Immunogenicity; Vaccine Efficacy; Colombia; Adult Volunteers

Outcome Measures

Primary Outcomes (1)

• Protective Efficacy Against P. vivax Infection After Controlled Human Malaria Infection (CHMI)

  Definition: Proportion of volunteers who develop P.vivax parasitemia following exposure to 2-4 infected Anopheles albimanus mosquitoes. Parasitemia will be assessed daily by thick blood smear (GG). PCR will be performed as a confirmatory assay but will not to be used for clinical decision-making. Unit of Measure: Number and percentage of infected participants.

  Day 7 to Day 28 post-challenge.

Secondary Outcomes (5)

• Incidence of Local Adverse Events at the Injection and Mosquito Bite Site Within 7 Days Post-Challenge

  Within 7 days post-challenge

• Incidence of Systemic Adverse Events Within 7 Days After Completion of Antimalarial Treatment

  Within 7 days post-challenge

• Incidence of Serious Adverse Events From First Vaccination Through 12 Months Post-Challenge

  From first vaccination through 12 months post-challenge

• Incidence of Laboratory Abnormalities in Hematology and Clinical Chemistry From Baseline to Day 60 Post-Challenge

  From baseline to Day 60 post-challenge

• Incidence of Coagulation and Urinalysis Abnormalities From Baseline to Day 60 Post-Challenge

  From baseline to Day 60 post-challenge

Other Outcomes (7)

• Anti-Plasmodium vivax Circumsporozoite Protein IgG Antibody Titers Measured by ELISA

  Day 0, Months 1, 2, 3, 6, 7, 8.

• Anti-sporozoite IgG Antibody Titers Measured by Indirect Fluorescent Antibody test (IFAT)

  Day 0, Months 1, 2, 3, 6, 7, 8.

• Interferon-Gamma-Producing T-cell Responses Measured by ELISpot Assay

  Day 0, Month 3, Month 6.

Study Arms (4)

Naïve Participants - PvCS/Montanide ISA-51 Vaccine

EXPERIMENTAL

Healthy adults with no prior malaria exposure will receive three intramuscular doses of the PvCS/Montanide ISA-51 VG vaccine at months 0, 2, and 4. The formulation contains a synthetic peptide representing the circumsporozoite protein (CS) of Plasmodium vivax combined with Montanide ISA-51 VG adjuvant. Participants will be monitored for safety and immune responses before undergoing controlled human malaria infection (CHMI) about one month after the final vaccination.

Biological: PvCS/Montanide ISA-51 VG Vaccine

Naïve Participants - Placebo

PLACEBO COMPARATOR

Healthy malaria-naïve adults will receive three intramuscular injections of placebo (adjuvant without PvCS antigen) on the same schedule as the vaccine arm (months 0, 2, and 4). Procedures for safety monitoring, blood sampling, and CHMI will be identical to those for the vaccine group. This arm serves as the negative control for efficacy and immunogenicity comparisons.

Biological: Placebo - Montanide ISA-51 VG Adjuvant Alone

Semi-Immune Participants - PvCS/Montanide ISA-51 Vaccine

EXPERIMENTAL

Adults with prior natural exposure to malaria will receive three intramuscular doses of the PvCS/Montanide ISA-51 VG vaccine at months 0, 2, and 4. Safety and immune parameters will be assessed throughout the vaccination phase. Approximately one month after the final dose, participants will undergo CHMI with P. vivax to determine vaccine-induced protection in semi-immune individuals.

Biological: PvCS/Montanide ISA-51 VG Vaccine

Semi-Immune Participants - Placebo

PLACEBO COMPARATOR

Semi-immune adults will receive three intramuscular injections of placebo (adjuvant without PvCS antigen) following the same schedule as the vaccinated groups. Participants will undergo the same clinical, laboratory, and parasitological monitoring during vaccination and CHMI. This arm provides comparative data for evaluating vaccine safety and efficacy in semi-immune populations.

Biological: Placebo - Montanide ISA-51 VG Adjuvant Alone

Interventions

PvCS/Montanide ISA-51 VG Vaccine BIOLOGICAL

The vaccine contains a synthetic peptide representing the central repeat and flanking regions of the Plasmodium vivax circumsporozoite (CS) protein, formulated with Montanide ISA-51 VG (Vaccine Grade), a water-in-oil adjuvant that enhances both antibody and T-cell responses. This formulation is distinct from other malaria vaccine candidates because it specifically targets P. vivax using a synthetic CS peptide antigen, rather than a recombinant protein or viral vector platform. Each 0.5-mL dose is administered intramuscularly in the deltoid at 0, 2, and 4 months. Participants will be closely monitored for safety, reactogenicity, and immunogenicity after each vaccination. Approximately one month after the final dose, volunteers will undergo a controlled human malaria infection (CHMI) via exposure to Anopheles albimanus mosquitoes infected with P. vivax sporozoites to assess protective efficacy.

Also known as: PvCS Synthetic Peptide Vaccine, PvCS/ISA-51 VG

Naïve Participants - PvCS/Montanide ISA-51 Vaccine; Semi-Immune Participants - PvCS/Montanide ISA-51 Vaccine

Placebo - Montanide ISA-51 VG Adjuvant Alone BIOLOGICAL

The placebo consists of Montanide ISA-51 VG (Vaccine Grade) adjuvant without the Plasmodium vivax circumsporozoite (CS) peptide antigen. It is a sterile water-in-oil emulsion prepared and administered in the same manner as the investigational vaccine to maintain blinding. Each 0.5-mL dose is given intramuscularly in the deltoid at 0, 2, and 4 months. The placebo is visually indistinguishable from the vaccine and follows identical handling, storage, and administration procedures. Participants in the placebo group will undergo the same safety monitoring, blood sampling, and controlled human malaria infection (CHMI) one month after the final dose to allow direct comparison of efficacy, safety, and immune responses.

Also known as: Naïve Participants - Placebo, Semi-Immune Participants - Placebo

Naïve Participants - Placebo; Semi-Immune Participants - Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able and willing to provide written informed consent prior to any study procedure.
• Available for the full duration of the study, including follow-up through 12 months post-challenge.
• Group-specific criteria:
• Malaria-naïve cohort: No prior malaria infection or residence in malaria-endemic areas; negative malaria serology at screening.
• Semi-immune cohort: Residence ≥ 5 years in a P. vivax-endemic area and documented or self-reported prior malaria exposure.
• Screening negative for HIV, hepatitis B surface antigen (HBsAg), and hepatitis C virus antibodies.
• For women of childbearing potential:
• Negative pregnancy test at screening and prior to each vaccination and/or CHMI. Commitment to use effective contraception (hormonal, IUD, barrier methods, or abstinence) from screening through the end of follow-up.
• Willingness to comply with all study procedures, including repeated blood sampling, controlled human malaria infection (CHMI), and inpatient or outpatient monitoring as required.

You may not qualify if:

• History of severe allergic reactions, including anaphylaxis, to vaccines or vaccine components such as Montanide ISA-51 VG, adjuvants, or synthetic peptides.
• Clinically significant acute or chronic medical conditions that may increase risk or interfere with study participation, including but not limited to:
• Cardiovascular disease Hepatic or renal impairment Neurological or psychiatric disorders Autoimmune diseases Hematologic abnormalities Immunodeficiency or immunosuppressive conditions Use of immunosuppressive therapies, systemic corticosteroids, antimalarial medications, or other agents that may interfere with vaccine immune responses within 30 days prior to enrollment.
• Receipt of immunoglobulins or blood products within 3 months prior to screening.
• Pregnancy or breastfeeding at screening or planned pregnancy during the study period.
• Participation in another clinical trial of an investigational product or device within 30 days prior to enrollment or planned participation during the study.
• Any clinically significant abnormality on screening laboratories, ECG, or physical examination that, in the investigator's judgment, could:
• Pose a safety risk, Confound study results, or Impair adherence to study procedures. Any condition or circumstance that, in the investigator's opinion, could compromise volunteer safety or the integrity of the trial.

Sponsors & Collaborators

• Johns Hopkins University: collaborator
• Malaria Vaccine and Drug Development Center: lead

Study Sites (1)

Malaria Vaccine and Drug Development Center (MVDC)

Cali, Valle del Cauca Department, 61000, Colombia

Location

MeSH Terms

Conditions

Malaria, Vivax

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Myriam Arevalo, PhD

  Malaria Vaccine and Drug Development Center (MVDC)

  STUDY DIRECTOR

Central Study Contacts

Dr. Myriam Arévalo Scientific Director MVDC, PhD

CONTACT

+ 57 317 5170557; marevalo@inmuno.org

Dr. Socrates Herrera Valencia Principal Investigator, MD

CONTACT

+ 57 3175170552; sherrera@inmuno.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Randomization and blinding procedures ensure that neither participants nor study staff involved in data collection or outcome assessment are aware of group allocation. Vaccine and placebo are identical in appearance and administration schedule.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study uses a randomized, double-blind, placebo-controlled, parallel-group design. Seventy-two healthy adults (18-50 years) from malaria-endemic areas of Chocó, Colombia, will be randomized 2:1 to receive PvCS/Montanide ISA-51 VG vaccine or placebo. Vaccinations will be given intramuscularly at 0, 2, and 4 months. One month after the final dose, all participants will undergo a controlled human malaria infection (CHMI) using Anopheles albimanus mosquitoes infected with Plasmodium vivax. Participants will be followed for infection, immune responses, and safety for up to 12 months

Study Record Dates

• First Submitted: November 13, 2025
• First Posted: January 28, 2026
• Study Start: January 19, 2026
• Primary Completion (Estimated): July 12, 2027
• Study Completion (Estimated): June 12, 2028
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: De-identified individual participant data and supporting documentation will be available after publication of the primary results of the study. Data may be requested for a period of up to five years following publication.
• Access Criteria: Access to de-identified individual participant data will be granted upon reasonable request to the corresponding investigator. Requests must include a research proposal and will be evaluated for scientific validity, ethical compliance, and consistency with participant consent. Approved users will receive access to de-identified data only, with no direct identifiers.

Locations

CO (1)